Herein, we report the synthesis of a biomimic hydrogel adhesive that addresses the poor healing of surgical anastomosis. Dopamine-conjugated xanthan gum (Da-g-Xan) is fabricated using deep insights into the molecular similarity between mussels' adhesive and dopamine as well as the structural similarity between barnacle cement proteins and xanthan gum. The hydrogel mimics marine animals’ adherence to wet tissue surfaces. Upon applying this adhesive to colonic anastomosis in a rat model, protective effects were shown by significantly improving the bursting pressure. Mechanistically, the architecture of Da-g-Xan hydrogel is maintained by dynamic intermolecular hydrogen bonds that allow the quick release of Da-g-Xan. The free Da-g-Xan can regulate the inflammatory status and induce type 2 macrophage polarization (M2) by specifically interacting with mannose receptors (CD206) revealed by RNA-sequencing and molecular binding assays. Consequently, an appropriate microenvironment for tissue healing is created by the secretion of chemokines and growth factors from M2 macrophages, strengthening the fibroblast migration and proliferation, collagen synthesis and epithelial vascularization. Overall, this study demonstrates an unprecedented strategy for generating an adhesive by synergistic mimicry inspired by two marine animals, and the results show that the Da-g-Xan adhesive augments native tissue regenerative responses, thus enabling enhanced recovery following surgical anastomosis.

Stimulator of interferons genes (STING) is an adaptor protein that plays a critical role in the secretion of type I interferons and pro-inflammatory cytokines in response to cytosolic nucleic acid. Recent research indicates the involvement of the STING pathway in uncontrolled inflammation, sepsis, and shock. STING signaling is significantly up-regulated in human sepsis, and STING agonists are sug-

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SummaryThe anti-digestive features given to hydrogels can prolong their action time in gut environment; however, these types of hydrogels have rarely been reported. Inspired by indigestibility of dietary fibers, we introduced an injectable covalent hydrogel through photopolymerization of glycidyl methacrylate-modified xanthan. This newly synthesized hydrogel exhibited a specific concentration-dependent porosity, swelling ratio, and stiffness. The intestinal epithelial cells-6 could grow on the surface of the stiffer hydrogel, and achieved their gut barrier functions. A simulated gut microfluidic chip was manufactured to demonstrate the hydrogel's good performance of anti-digestion compared with the current product, fibrin sealant. Furthermore, calcium ions could induce the swelling-shrinking behavior of the hydrogel, which assisted in removing the hydrogels at the proper time so as to avoid the mismatch of hydrogel degradation and tissue regeneration. Therefore, this hydrogel is expected to be an outstanding gut repair material, especially for closing gastrointestinal fistula.

The gastrointestinal (GI) tract has a diverse set of physiological functions, including peristalsis, immune defense, and nutrient absorptions. These functions are mediated by various intestinal cells such as epithelial cells, interstitial cells, smooth muscle cells, and neurocytes. The loss or dysfunction of specific cells directly results in GI disease, while supplementation of normal cells promotes gut healing. Gut bioengineering has been developing for this purpose to reconstruct the damaged tissues. Moreover, GI tract provides an accessible route for drug delivery, but the collateral damages induced by side effects cannot be ignored. Bioengineered intestinal tissues provide three-dimensional platforms that mimic the in vivo environment to study drug functions. Given the importance of gut bioengineering in current research, in this review, we summarize the advances in the technologies of gut bioengineering and their applications. We were able to identify several ground-breaking discoveries in our review, while more work is needed to promote the clinical translation of gut bioengineering.

As an emerging technology, intestinal organoids are promising new tools for basic and translational research in gastroenterology. Currently, culture of intestinal organoids relies mostly on a type of tumor-derived scaffolds, namely Matrigel, which may pose tumorigenic risks to organoid implantation. Apart from the traditional detection methods, such as tissue slicing and fluorescence staining, the monitoring of intestinal organoids requires real-time biosensors that can adapt to their threedimensional dynamic growth patterns. In this review, we summarized the recent advances in developing definite hydrogel scaffolds for intestinal organoid culture and identified key parameters for scaffold design. In addition, classified by different substrate compositions like pH, electrolytes, and functional proteins, we concluded the existing live-imaging biosensors and elucidated their underlying mechanisms. We hope this review enhances the understanding of intestinal organoid culture and provides more practical approaches to investigate them. K E Y W O R D Sbiosensor, intestinal stem cell, organoid, regenerative medicine, scaffold design

Background. The gut was suggested as the driver of critical illness and organ injury. Recently, excessive formation of neutrophil extracellular traps (NETs) was associated with mucosal inflammation. Direct investigation of intestinal mucosa is essential to illuminate the potential mechanism of gut barrier in critically ill patients. We hypothesized that early enteral nutrition (EN) could decrease intestinal NETs and maintain the gut barrier. Methods. Intestinal biopsies were obtained using biopsy forceps from critically ill surgical patients complicated with enterocutaneous fistula. Expressions of tight junction (TJ) proteins, mucosal inflammation, and apoptosis were evaluated. Moreover, NET-associated proteins were evaluated in intestinal specimens of patients by Western blot and immunofluorescence analysis. Results. The intestinal barrier was significantly impaired in critically ill patients receiving early total parenteral nutrition (TPN), evidenced by intestinal villi atrophy, inflammatory infiltration, increased enterocyte apoptosis, and abnormal TJ expressions. Early EN significantly alleviated these intestinal injuries. In addition, we observed increased formation of the NET structure and elevated expressions of NET-associated proteins in intestines of critically ill surgical patients. Early EN was associated with the diminished presence of NETs and reduced expression of NET-associated proteins. Mechanically, analysis of the TLR4 pathway showed a significant increase in TLR4, NFκB, and MAPK signaling in patients receiving TPN when compared to those receiving early EN. Conclusion. The intestinal barrier is disrupted in the human gut during critical illness. Our data suggests that an increased NET structure was showed in the gut of critically ill surgical patients, and early EN treatment was associated with the reduction of NET formation and the preservation of mucosal immunity.

Purpose To develop deep learning models based on color fundus photographs that can automatically grade myopic maculopathy, diagnose pathologic myopia, and identify and segment myopia-related lesions. Methods Photographs were graded and annotated by four ophthalmologists and were then divided into a high-consistency subgroup or a low-consistency subgroup according to the consistency between the results of the graders. ResNet-50 network was used to develop the classification model, and DeepLabv3+ network was used to develop the segmentation model for lesion identification. The two models were then combined to develop the classification-and-segmentation–based co-decision model. Results This study included 1395 color fundus photographs from 895 patients. The grading accuracy of the co-decision model was 0.9370, and the quadratic-weighted κ coefficient was 0.9651; the co-decision model achieved an area under the receiver operating characteristic curve of 0.9980 in diagnosing pathologic myopia. The photograph-level F 1 values of the segmentation model identifying optic disc, peripapillary atrophy, diffuse atrophy, patchy atrophy, and macular atrophy were all >0.95; the pixel-level F 1 values for segmenting optic disc and peripapillary atrophy were both >0.9; the pixel-level F 1 values for segmenting diffuse atrophy, patchy atrophy, and macular atrophy were all >0.8; and the photograph-level recall/sensitivity for detecting lacquer cracks was 0.9230. Conclusions The models could accurately and automatically grade myopic maculopathy, diagnose pathologic myopia, and identify and monitor progression of the lesions. Translational Relevance The models can potentially help with the diagnosis, screening, and follow-up for pathologic myopic in clinical practice.